Trypanosomal parasites, such as Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei), utilize glycolysis which is an essential energy-producing metabolic pathway. Since glycolysis is indispensable for these organisms, obstruction of the pathway leads to cell death and can be caused by inhibition (using a drug) of two similar enzymes, hexokinase and glucokinase. In order to create a therapeutic drug, an inhibitor would need to selectively block the parasite homologue and avoid cross-reactivity with the human homologue (bind weaker or not bind at all), giving rise to a good selectively ratio.
Chagas' disease has two standard-of-care treatments available, such as benznidazole and nifurtimox, which were developed over 35 years ago. African sleeping sickness has been reliant on a variety of drugs, such as pentamidine, suramin, eflornithine, and melarsoprol; however, all of these medicines (for both diseases) require substantial improvements in their tolerability, safety, and efficacy. Additionally, many of the currently available drugs for treatment are ineffective due to low cellular penetration with the drugs bearing phosphate or phosphonate groups.
As such, a need exists for new inhibitors of the enzymes hexokinase and glucokinase.